Upregulation of CD44 attenuates hypoxia/reoxygenation-induced ferroptosis and injury in cardiomyocytes by CD44/SLC7A11 pathway

Upregulation of CD44 attenuates hypoxia/reoxygenation-induced ferroptosis and injury in cardiomyocytes by CD44/SLC7A11 pathway | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 28 January 2025 V1 Latest version Share on Upregulation of CD44 attenuates hypoxia/reoxygenation-induced ferroptosis and injury in cardiomyocytes by CD44/SLC7A11 pathway Authors : xia huang 0009-0007-6772-7166 , Tingting Xue , Xiangrong Cui 0000-0001-6328-6526 , Yanni Wang , Qin Yan , Shu Wang , Xinyu Zhu , Huihui Li 0009-0006-7215-8028 , Fuheng Chen , Yifei Zhang , and Xuan Jing [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.173808937.71296341/v1 189 views 66 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background: Even though advanced technologies for interventional coronary reperfusion after myocardial infarction have been developed, reperfusion leads to various forms of cell death and thus worsens cardiac functions. Ferroptosis, a novel regulated cell death characterized by iron overload and reactive oxygen species(ROS) accumulation, involved in myocardial ischemia/reperfusion(I/R) injury. However, the role of ferroptosis in ischemia phase and reperfusion phase remains unclear, and key regulatory mechanisms of ferroptosis still need further exploration in the context of myocardial I/R injury. Methods: Myocardial I/R injury database GSE160516 downloaded from the Gene Expression Omnibus (GEO) database and ferroptosis-related genes (FRGs) obtained from the FerrDb database ([https://www.zhounan.org/ferrdb](https://www.zhounan.org/ferrdb)) were used to screen differentially expressed ferroptosis-related genes(DEFRGs). To identify crucial hub gene involved in cardiomyocyte ferroptosis, LASSO regression and SVM-RFE Algorithms were used. Venous blood samples were collected from acute myocardial infarction (AMI) patients on the first day after admission and within 48 h after percutaneous coronary intervention (PCI) to explore CD44 expression and its correlation with prognostic indicators. Moreover, a AC16 cardiomyocyte oxygen-glucose deprivation/reoxygenation (OGD/R) model was performed to verify the expression of CD44 and the role of ferroptosis in ischemia phase and reperfusion phase. Loss -of-function approaches was conducted to understand the role of CD44 in ferroptosis and explore the mechanisms in myocardial I/R injury. Result: Trough integrated bioinformatics analysis, CD44 was identified as the hub gene of ferroptosis, and significantly upregulated in myocardial I/R injury. In AC16 OGD/R model, the mRNA and protein levels of CD44 were significantly upregulated during the reoxygenation phase, but not the hypoxia phase. AMI patients of post-PCI had higher serum CD44 expression compared to those who did not undergo percutaneous coronary intervention(PCI) and healthy individuals. Serum CD44 levels of post-PCI was closely correlated with adverse prognostic indicators of MI. In additional, we found that reoxygenation further induce the development of ferroptosis. Knockdown of CD44 markedly aggravate cardiomyocyte injury and induced ferroptosis by CD44/SLC7A11 axis. Conclusion: Our results uncover the cardioprotective role of CD44 by attenuating hypoxia/reoxygenation-induced ferroptosis and injury. Targeting CD44-intiated signaling may serve as a promising therapeutic target for myocardial I/R injury. Supplementary Material File (figure6.pdf) Download 20.22 MB File (manuscript.docx) Download 135.93 KB File (table1.docx) Download 19.39 KB Information & Authors Information Version history V1 Version 1 28 January 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Authors Affiliations xia huang 0009-0007-6772-7166 Fifth Hospital of Shanxi Medical University View all articles by this author Tingting Xue Fifth Hospital of Shanxi Medical University View all articles by this author Xiangrong Cui 0000-0001-6328-6526 Second Hospital of Shanxi Medical University View all articles by this author Yanni Wang Fifth Hospital of Shanxi Medical University View all articles by this author Qin Yan Second Hospital of Shanxi Medical University View all articles by this author Shu Wang Fifth Hospital of Shanxi Medical University View all articles by this author Xinyu Zhu Fifth Hospital of Shanxi Medical University View all articles by this author Huihui Li 0009-0006-7215-8028 Second Hospital of Shanxi Medical University View all articles by this author Fuheng Chen Fifth Hospital of Shanxi Medical University View all articles by this author Yifei Zhang Fifth Hospital of Shanxi Medical University View all articles by this author Xuan Jing [email protected] Fifth Hospital of Shanxi Medical University View all articles by this author Metrics & Citations Metrics Article Usage 189 views 66 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation xia huang, Tingting Xue, Xiangrong Cui, et al. Upregulation of CD44 attenuates hypoxia/reoxygenation-induced ferroptosis and injury in cardiomyocytes by CD44/SLC7A11 pathway. Authorea . 28 January 2025. DOI: https://doi.org/10.22541/au.173808937.71296341/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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